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Biochemistry (Moscow)

, Volume 82, Issue 7, pp 826–833 | Cite as

Omega-3 polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid enhance dexamethasone sensitivity in multiple myeloma cells by the p53/miR-34a/Bcl-2 axis

  • Xianping DaiEmail author
  • Mengshun Li
  • Feng Geng
Article

Abstract

Dexamethasone is widely used in multiple myeloma (MM) for its cytotoxic effects on lymphoid cells. However, many MM patients are resistant to dexamethasone, although some can benefit from dexamethasone treatment. In this study, we noted that ω-3 polyunsaturated fatty acids (PUFAs) enhanced the dexamethasone sensitivity of MM cells by inducing cell apoptosis. q-PCR analysis revealed that miR-34a could be significantly induced by PUFAs in U266 and primary MM cells. Transfection with miR-34a antagonist or miR-34a agomir could restore or suppress the dexamethasone sensitivity in U266 cells. Both luciferase reporter assay and Western blot showed that Bcl-2 is the direct target of miR-34a in MM cells. In addition, we observed that PUFAs induced p53 protein expression in MM cells under dexamethasone administration. Furthermore, suppressing p53 by its inhibitor, Pifithrin-α, regulated the miR-34a expression and modulated the sensitivity to dexamethasone in U266 cells. In summary, these results suggest that PUFAs enhance dexamethasone sensitivity to MM cells through the p53/miR-34a axis with a likely contribution of Bcl-2 suppression.

Keywords

polyunsaturated fatty acids eicosapentaenoic acid docosahexaenoic acid dexamethasone apoptosis miR-34a p53 Bcl-2 

Abbreviations

Dex

dexamethasone

DHA

docosahexaenoic acid

EPA

eicosapentaenoic acid

MM

multiple myeloma

MTT (test)

3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide

PFTa

Pifithrin-α

PI

propidium iodide

PUFAs

ω-3 polyunsaturated fatty acids

UTR

untranslated region

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Copyright information

© Pleiades Publishing, Ltd. 2017

Authors and Affiliations

  1. 1.Binzhou Medical University, School of PharmacyYantai, ShandongChina

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